tbuckley/cabot-search huggingface dataset:
The controversial abscopal effect: A single-center experience about the combination of stereotactic radiotherapy with pembrolizumab in patients with metastatic dMMR/MSI-H colorectal cancer.
Authors: Annalice Gandini, Valentino Martelli, Liliana Belgioia, Silvia Puglisi, Malvina Cremante, Veronica Murianni, Alessandra Damassi, Ilaria Ricciotti, Chiara Pirrone, Fabio Catalano, Massimiliano Grassi, Anna Maria Pessino, Alessandro Pastorino, Stefania Sciallero, Alberto Puccini, Alberto F. Sobrero
Journal: Journal of Clinical Oncology (2023)

2608 Background: Colorectal cancer (CRC) patients with mismatch repair system deficiency (dMMR/MSI-H) have shown impressive responses to immune checkpoint inhibitors in any lines of treatment. However, almost 30% of these patients are primary refractory and another 30% develop secondary resistance. Thus, many treatment combinations are being pursued to overcome resistance. One of the proposed strategies is the addition of radiotherapy to immunotherapy based on the potential abscopal effect and its consequent on-target and off-target activity. Methods: Between November 2019 and April 2021, we conducted a prospective interventional single-institution study to assess the feasibility, disease control and safety of the combination of pembrolizumab with stereotactic ablative radiotherapy (SABR) in a cohort of 14 consecutive dMMR CRC patients. SABR was administered in combination within the second or third cycle of Pembrolizumab 200 mg infused every 21 days. SABR was delivered on one or more targetable metastases with the ablative dose of 15 Gy in the first fraction followed by a second fraction of 5 Gy. Results: Fourteen patients were enrolled and 11 received radiotherapy in combination with Pembrolizumab as per protocol. Three patients who started Pembrolizumab never received radiotherapy due to deterioration of their general conditions, leading to death within two months. Two out of these three patients were BRAF V600E mutated. Five patients (35.7%) received Pembrolizumab as first line, 6 (43%) as second line and 3 (21%) as third or later lines. Six out of 14 patients (42.9%) harboured BRAF V600E mutation, 2 out of 14 (14.3%) RAS mutation and the others were RAS/BRAF wild type. Objective response was observed in 4 out of 14 patients (29%) and disease control was achieved in 7/14 patients (50%). Among these, six patients (42%) achieved a disease control lasting more than 15 months. This regimen caused substantial toxicity, mainly linked to SABR. Any grade TRAEs occurred in 50% of patients, with one patient with G1 event, three patients with G2 events, and two patients with G3 events (pneumonia, bowel perforation); no treatment-related deaths were observed. Conclusions: These data do not show hint of added efficacy of Pembrolizumab by SART in unresectable dMMR/MSI-H mCRC.
A phase (Ph) I/II trial of abiraterone acetate in combination with tildrakizumab (anti-IL23 monoclonal antibody) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Christina Guo, Simon J. Crabb, Simon Pacey, Vicky Coyle, Sarah Danson, Guillermo Villacampa, Khobe Chandran, Alec Paschalis, Ruth Riisnaes, Ana Ferreira, Suzanne Carreira, Claudia Bertan, Mateus Crespo, Ines Figueiredo, Ruth Matthews, Alison Joanne Turner, Christina Yap, Andrea Alimonti, Adam Sharp, Johann S. De Bono
Journal: Journal of Clinical Oncology (2023)

TPS5105 Background: Tumor-infiltrating inflammatory myeloid cells promote prostate cancer (PC) growth and therapeutic resistance. Myeloid inflammatory cells release interleukin-23 (IL-23) to fuel tumor growth via JAK2-STAT3 signalling and facilitate tumor-promoting T helper 17 (T H 17) differentiation in PC models in vivo. IL-23 blockade reverses resistance to AR-targeting in vivo; we hypothesise that targeting IL-23 can be an effective therapeutic strategy for CRPC. Tildrakizumab, an anti-IL-23 (p19) monoclonal antibody, is FDA/EMA approved for treating moderate-severe psoriasis. In progress is the first clinical trial to combining IL-23 and AR signalling blockade in humans. Methods: This is an open-label, single-arm, Ph 1/2, dose-escalation and expansion study evaluating safety and tolerability of tildrakizumab and abiraterone acetate combination therapy in patients with mCRPC. Eligible patients must have progressed on androgen deprivation therapy, plus abiraterone and/or enzalutamide. The Ph 1 trial will adopt a one-stage Bayesian Continual Reassessment Method design exploring escalating doses of 4-weekly, IV tildrakizumab (100 mg, 300 mg, and 600 mg), in combination with standard fixed doses of abiraterone acetate and methylprednisolone, with the aim of determining the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Depending on the number of responses observed, tolerable dose levels may be expanded up to 10 patients after review by the Safety Review Committee (SRC). The RP2D and MTD determination will be based on the rate of toxicity and efficacy, reviewed by the SRC. Once RP2D is determined, the Ph 2 study will enrol up to 25 response-evaluable patients using a Simon’s two-stage design. Primary endpoint of the Ph 2 trial is overall response rate. Adverse events are assessed according to CTCAE v5. Tumor response is determined according to RECIST v1.1, confirmed PSA decline of at least 50%, and/or CTC conversion. PK analyses is being performed for both drugs to identify potential drug-drug interactions. PD analyses is being performed on archival and serial tumour biopsies and blood samples to investigate putative predictive biomarkers and confirm on-target and downstream effector modulation. The trial began enrolling in January 2021 in the United Kingdom and Switzerland. As of January 22th 2023, 12 patients were included in the study. Clinical trial information: NCT04458311 .
A phase II study of regorafenib plus sintilimab as salvage-line treatments in non–MSI-H metastatic colorectal cancer (mCRC).
Authors: Rui Liu, Zhi Ji, Xia Wang, Le Zhang, Yuchong Yang, Tao Ning, Shaohua Ge, Hongli Li, Ming Bai, Ting Deng, Yi Ba
Journal: Journal of Clinical Oncology (2023)

3562 Background: PD-1 blockade is particularly ineffective in patients with microsatellite stable (MSS) or mismatch repair (MMR)-proficient colorectal cancer (CRC). Regorafenib (R) has been shown to modulate anti-tumor immunity by different mechanisms including reduction of tumor-associated macrophages (TAMs) and the immunosuppressive cells. Synergy between Regorafenib and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical models, as well as in several clinical studies, compared with either treatment alone. The purpose of this study was to evaluate the activity of regorafenib in combination with immune checkpoint inhibitors. Methods: This is a single-arm, open-label, phase II trial assessing the efficacy and safety of Regorafenib (80mg QD 3weeks/4) + Sintilimab (S) (200mg every 3 weeks) combination in non MSI-H mCRC patients (pts). The primary endpoint was the overall survival (OS). Secondary endpoints included progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and Safety. Results: As of February 1, 2023, a total of 103 patients with mCRC were enrolled and received R+S. Median age was 57 (range, 28-75). Male 59.2%, ECOG PS 0/1/2 20.4%/66.0%/13.6%, left-sided colon/right-sided colon/rectum 39.8%/15.5%/44.7%, RAS mutant 42.7%. The ORR was 21.4% and DCR was 63.1%, with complete response (cCR) in 1 (1.0%), partial response (PR) in 21 (20.4%) and stable disease (SD) in 43 (41.7%) patients. With a median follow up of 19.9 months (range, 0.1-41.4), the median PFS was 4.0 months (95% CI, 3.1-4.4 months) and median OS was 13.0 months (95% CI, 12.0-16.5 months). The patients who achieved ORR have significantly longer PFS (20.8 vs. 3.2 months, p＜0.001) and OS (not reach vs. 12.0 months, p＜0.001) than the non-ORR patients. The median PFS were similar regardless the KRAS mutation status, primary sidedness, or liver metastases. Multivariate analysis revealed that male, ECOG PS2, the number of metastatic sites ≥2, and RAS mutant were significantly associated with worse OS. The most common grade 3/4 adverse events were hand-foot syndrome (1.9%), stomatitis (1.9%), rash (1.0%), hypertension (1.0%), allergic reaction (1.0%), fatigue (1.0%) and fever (1.0%). 8(7.8%) patients experienced at least 1 dose modification or treatment interruption. No death was related to the treatment. Conclusions: In this study the R+S combination as salvage-line treatments in non-MSI-H mCRC achieved a promising clinical benefit, with a manageable safety profile. Female, ECOG PS0/1, single metastases, RAS wild type mCRC were associated with better OS. Clinical trial information: NCT04745130 .
A combination of niraparib plus anlotinib in patients with platinum-resistant ovarian clear cell carcinoma: Results of a single-arm phase II study (CC-ANNIE study).
Authors: Shaodan Lin, Ming Gao, Jing Li, Lijuan Wang, Zhong-qiu Lin, Bingzhong Zhang
Journal: Journal of Clinical Oncology (2023)

e17552 Background: Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer with distinct biological and molecular characteristics. Patients with platinum-resistant OCCC have a poor prognosis and their treatment represents a significant unmet medical need. Studies have suggested potential efficacy of targeting DNA damage response pathways and inhibition of angiogenesis in OCCC. We hypothesised that patients with platinum-resistant OCCC might benefit from a combination of the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib and the anti-angiogenic agent anlotinib. Methods: This was a phase II, single-arm, two-stage study with a Simon’s two-stage optimal design. The trial could continue to stage 2 if ≥1 responses were observed in the first 6 patients. Eligible patients had histologically confirmed OCCC that was platinum resistant, defined as progression within 6 months after their most recent platinum-based chemotherapy. Use of prior bevacizumab was permitted but prior PARP inhibitor or tyrosine kinase inhibitor treatments were not. Patients received niraparib (300 mg/day or 200 mg/day [baseline body weight &lt; 77 kg, platelet count &lt; 150,000/μL], orally) plus anlotinib (10 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) assessed by investigators according to the RECIST V.1.1. Secondary endpoints included disease control rate (DCR), time to response (TOR), duration of response (DOR), safety and investigator-assessed progression-free survival (PFS) and overall survival (OS). Results: Between January 2022 and August 2022, 6 eligible patients were enrolled and included in the analyses. The median duration of treatment was 9.8 (range, 6.5 to 19.0) weeks. Of the 6 patients, 0 patients (0%) achieved an objective response, resulting in a confirmed ORR of 0%. The DCR was 50% (0 complete response, 0 partial response, 3 stable disease). With a median follow-up time of 7.5 (range, 3.5 to 10.0) months, all patients experienced disease progression, with a median PFS of 12.0 (95% confidence interval [CI], 3.6 to 20.4) weeks. Frequent treatment-related adverse events (AEs) included hypertension (33.3%), thrombocytopenia (33.3%), and hand-foot syndrome (16.6%). Conclusions: The phase 2 CC-ANNIE study did not meet the primary efficacy endpoint. The combination of niraparib and anlotinib did not show activity in patients with platinum-resistant OCCC. Clinical trial information: NCT05130515 .
The impact of anti-EGFR therapy when added to first-line standard platinum-gemcitabine chemotherapy in advanced biliary tract cancers: A meta-analysis of randomized studies.
Authors: Dawood Findakly, Philip A. Haddad
Journal: Journal of Clinical Oncology (2023)

e16109 Background: Biliary tract cancers (BTCs) represent the second-most common primary liver cancers. They are a heterogeneous group of tumors that include Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, and ampullary carcinoma. BTCs are usually diagnosed in an advanced stage and carry a poor prognosis. A better understanding of cancer biology has led to advances in targeted treatments in other cancers but remains an unmet need in BTCs. We conducted this meta-analysis to evaluate the efficacy of anti-EGFR therapy when added to the standard platinum-gemcitabine chemotherapy as first-line in patients with advanced BTCs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of biliary tract tumors, randomized studies of first-line platinum-gemcitabine with and without anti-EGFR therapies, and studies that reported overall (OS) and progression free survival (PFS). A meta-analysis using the fixed effects and random effects models was conducted. Results: Four randomized studies with a total of 569 patients were included. Three studies were randomized phase 2 and one was randomized phase 3. Three studies used oxaliplatin and one used cisplatin in addition to gemcitabine as the standard combination. Panitumumab was used in two studies while cetuximab and erlotinib were used in one study each. The addition of anti-EGFR agent to first-line platinum-gemcitabine in advanced BTC resulted in a superior OS (HR = 0.72, 95%CI 0.61-0.85) and PFS (HR = 0.76, 95%CI 0.63-0.92). When the analysis was restricted to anti-EGFR monoclonal antibodies, their PFS benefit persisted (HR = 0.72, 95%CI 0.55-0.95), but their OS benefit failed to reach statistical significance (HR = 0.83, 95%CI 0.65-1.07). Conclusions: This is the first meta-analysis to show the addition of anti-EGFR agents to the standard first-line platinum-gemcitabine chemotherapy improves OS and PFS in advanced BTC.
The effect of touch on pain, anxiety, and the patient experience during bone marrow biopsies.
Authors: Natasha Dhawan, Anna Schaal, Jacob R. Pushee, Kathleen Broglio
Journal: Journal of Clinical Oncology (2023)

e24131 Background: Many patients report severe pain and anxiety during bone marrow biopsies (BMBx), but there is no formal consensus on the best approach to managing these symptoms during the procedure. The aims of this study were to evaluate the effect of simple foot touch on pain and anxiety during BMBx, and to describe the patients’ experience during the procedure. Methods: A single-center randomized control trial using permuted block randomization was conducted at a rural academic cancer center. Nursing assistants without specialized massage training performed simple foot touch on patients in the intervention arm, while the BMBx was performed by advanced practice registered nurses. The patients in the control arm received usual care. Patients rated pain and anxiety levels before and after BMBx using the Visual Analog Scale (VAS) and Spielberger State-Trait Anxiety Inventory (STAI) scales, respectively. All participants completed a post-intervention survey about their experience. Results: 46 patients were enrolled in the study; 21 in the intervention arm (median age 64.1 years) and 25 in the control arm (median age 64.4 years). There was no difference in the use of anxiolytics (p = 0.51) or opioids (p = 0.48) during the procedure between the two arms. There were no statistically significant differences on the VAS (p = 0.37) or STAI (p = 0.40) between the intervention and control arms. Participants in the intervention arm reported more positive feedback and had fewer suggestions for improving the patient experience compared to the control arm (table 1). Conclusions: This is the first study to use an interprofessional team approach to evaluate the impact of touch on pain, anxiety, and the patient experience during BMBx. While the intervention did not impact pain or anxiety scores, it may be a feasible, minimal-risk, and no-cost intervention to improve patients’ overall experience during BMBx. Clinical trial information: NCT04935775 . [Table: see text]
Clinical outcomes with neoadjuvant nivolumab (N) + chemotherapy (C) vs C by definitive surgery in patients (pts) with resectable NSCLC: 3-y results from the phase 3 CheckMate 816 trial.
Authors: Jonathan Spicer, Patrick M. Forde, Mariano Provencio, Shun Lu, Changli Wang, Tetsuya Mitsudomi, Stephen Broderick, Scott Swanson, Mark M. Awad, Enriqueta Felip, Julie R. Brahmer, Keith Kerr, Gene Brian Saylors, Ke-Neng Chen, Fumihiro Tanaka, Junliang Cai, Javed Mahmood, Nan Hu, Phuong Tran, Nicolas Girard
Journal: Journal of Clinical Oncology (2023)

8521 Background: In CheckMate 816, neoadjuvant N + C demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) vs C in pts with resectable NSCLC. Here, we report clinical outcomes in pts with or without definitive surgery following neoadjuvant treatment (tx). Methods: Adults with stage IB (tumors ≥ 4 cm) to IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ ALK mutations were randomized 1:1 to 3 cycles of N 360 mg + C Q3W or C Q3W, followed by definitive surgery within 6 wk of tx. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS (secondary definition; no censoring for subsequent tx), time to death or distant metastasis (TTDM), and EFS2 (EFS on next-line tx) in pts with or without surgery. Results: Among 358 randomized pts, 149 (83%; N + C) and 135 (75%; C) had definitive surgery. Baseline characteristics were similar in pts with or without surgery (N + C, 30; C, 44) and between tx arms, except that a higher proportion of pts who did not have surgery had ECOG PS 1 (both arms) or were from Europe (N + C arm). Surgery was canceled due to progressive disease (PD) in 11 (N + C) and 17 (C) pts; PD was locoregional in 4 and 15 pts and distant in 3 and 2 pts, while 4 pts in the N + C arm had both locoregional and distant PD. At database lock (October 14, 2022; median f/u: 41.4 mo), EFS, TTDM, and EFS2 were numerically improved in pts with vs without surgery, regardless of tx arm. In pts with surgery, median TTDM was not reached (NR) vs 46.8 mo (HR, 0.55) with N + C vs C, respectively; 3-y TTDM rates were 77% vs 59%. In pts without surgery, median TTDM was 24.8 vs 15.6 mo (HR, 0.63) with N + C vs C; 3-y rates were 36% vs 13%. Among pts without surgery, 17 (57%) vs 28 (64%) pts in the N + C vs C arms, respectively, received subsequent tx: radiotherapy 37% vs 41%; surgery 3% vs 2%; systemic tx 50% vs 52%. Grade 3/4 tx-related AEs occurred in 38% (N + C) and 36% (C) in pts with surgery, and 26% and 46% in pts without surgery. Conclusions: In CheckMate 816, neoadjuvant N + C demonstrated long-term clinical benefit vs C in pts with resectable NSCLC who received definitive surgery. In pts who did not receive definitive surgery, these exploratory analyses showed that neoadjuvant N + C was associated with numerically improved TTDM. Clinical trial information: NCT02998528 . [Table: see text]
The role of MIBG scan in the diagnosis of pheochromocytoma.
Authors: Cherifa Fazila Ghomari, Abdelkader Medjahedi
Journal: Journal of Clinical Oncology (2023)

e15064 Background: Pheochromocytoma is an uncommon adrenal medulla tumor. Metaiodobenzylguanidine (MIBG) scintigraphy is the current gold standard functional imaging method for evaluating pheochromocytoma, due to its excellent 100% specificity, 80% sensitivity, and general availability. In addition to establishing an extension evaluation and monitoring medication efficacy, MIBG scintigraphy is essential to confirm the diagnosis of suspected pheochromocytoma, especially when there is a tumor-like adrenal mass whose etiology is to be determined and biopsy is contraindicated given the risk of catecholamine discharge with hypertensive flare and the risk of bleeding. Our aims are to determine the efficacy of scintigraphy in the diagnosis of pheochromocytoma by examining the epidemiological characteristic and uptake patterns of the disease. Methods: In a retrospective analysis from January 2010 to December 2020, we examined pheochromocytoma patients medical records who had been referred for MIBG scintigraphy to the regional western Algerian Nuclear Medicine department at the University Hospital Center of Tlemcen. Prior to a progressive intravenous injection of 40–80 MBq of l-MIBG, patients underwent preparation (discontinuation of interfering drugs with I-MIBG especially antihypertensive treatment, thyroid blocking, and hydration). Imaging acquisition was carried out 48 and 72 hours later. Results: Fifty patients with probable pheochromocytoma (sex ratio = 0,78; mean age = 43 [17-74] years) completed I-MIBG scintigraphy prior to adrenalectomy. The MIBG scan has a high specificity and positive predictive value (100%). It confirms the presence of pheochromocytoma in 21 cases (42%), even if the metanephrine is normal in a patient with a non-secreting pheochromocytoma. In 18 cases, the main pattern is a single, homogenous, and intense intra-abdominal uptake. For the three remaining patients, a voluminous and heterogeneous uptake with a photopenic center that was associated to a necrotic adrenal mass larger than 10 cm in size, seen on abdominal Computerized Tomography (CT). In this retrospective analysis, no cases of metastatic or multiple diseases were documented. The sensitivity and negative predictive value are 84% and 86%, respectively. In 29 patients (58%), the scan reveals no abnormalities in uptake. This is attributed, in part, to 30% false positive biology (sampling conditions of urinary and/or plasmatic metanephrines and/or normetanephrines), 20% false positive CT imaging (differential diagnosis of adrenal mass: benign or malignant adrenal nodule), and 8% false negative MIBG scintigraphy (subcentimetric, cystic and necrotic lesion). Conclusions: Due to its exceptional specificity, robust sensitivity, and whole-body staging, MIBG scintigraphy—along with biology and morphology imaging—is a crucial noninvasive diagnostic method for the management of pheochromocytoma prior to adrenalectomy.